Self-assembling lipopeptides with a potent activity against Gram-positive bacteria, including multidrug resistant strains

ABSTRACT RWJ-54428 (MC-02,479) is a new cephalosporin with a high level of activity against gram-positive bacteria. In a broth microdilution susceptibility test against methicillin-resistant Staphylococcus aureus (MRSA), RWJ-54428 was as active as vancomycin, with an MIC at which 90% of isolates are inhibited (MIC90) of 2 μg/ml. For coagulase-negative staphylococci, RWJ-54428 was 32 times more active than imipenem, with an MIC90 of 2 μg/ml. RWJ-54428 was active against S. aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus isolates with reduced susceptibility to glycopeptides (RWJ-54428 MIC range, ≤0.0625 to 1 μg/ml). RWJ-54428 was eight times more potent than methicillin and cefotaxime against methicillin-susceptible S. aureus (MIC90, 0.5 μg/ml). For ampicillin-susceptible Enterococcus faecalis (including vancomycin-resistant and high-level aminoglycoside-resistant strains), RWJ-54428 had an MIC90 of 0.125 μg/ml. RWJ-54428 was also active against Enterococcus faecium, including vancomycin-, gentamicin-, and ciprofloxacin-resistant strains. The potency against enterococci correlated with ampicillin susceptibility; RWJ-54428 MICs ranged between ≤0.0625 and 1 μg/ml for ampicillin-susceptible strains and 0.125 and 8 μg/ml for ampicillin-resistant strains. RWJ-54428 was more active than penicillin G and cefotaxime against penicillin-resistant, -intermediate, and -susceptible strains ofStreptococcus pneumoniae (MIC90s, 0.25, 0.125, and ≤0.0625 μg/ml, respectively). RWJ-54428 was only marginally active against most gram-negative bacteria; however, significant activity was observed against Haemophilus influenzae andMoraxella catarrhalis (MIC90s, 0.25 and 0.5 μg/ml, respectively). This survey of the susceptibilities of more than 1,000 multidrug-resistant gram-positive isolates to RWJ-54428 indicates that this new cephalosporin has the potential to be useful in the treatment of infections due to gram-positive bacteria, including strains resistant to currently available antimicrobials.

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Antimicrobial Diterpenes from Azorella Species against Gram-Positive Bacteria

Natural Product Communications ◽

10.1177/1934578x1501001127 ◽

2015 ◽

Vol 10 (11) ◽

pp. 1934578X1501001 ◽

Cited By ~ 2

Author(s):

Viviana Donoso ◽

Mitchell Bacho ◽

Solange Núñez ◽

Juana Rovirosa ◽

Aurelio San-Martín ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Mycobacterium Smegmatis ◽

Antimycobacterial Activity ◽

Multidrug Resistant ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Resistant Strains ◽

Andean Plants

The present study was aimed at evaluating the antibacterial activity of mulinane and azorellane diterpenes isolated from the Andean plants Azorella compacta and A. trifoliolata and semisynthetic derivatives against reference and multidrug-resistant strains. The results revealed that the semisynthetic compound 7-acetoxy-mulin-9,12-diene (5) exhibited antibacterial activity against reference and multidrug-resistant strains of Staphylococcus aureus and moderate antimycobacterial activity against Mycobacterium smegmatis ATCC 14468.

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Chromone Derivatives and Other Constituents from Cultures of the Marine Sponge-Associated Fungus Penicillium erubescens KUFA0220 and Their Antibacterial Activity

Marine Drugs ◽

10.3390/md16080289 ◽

2018 ◽

Vol 16 (8) ◽

pp. 289 ◽

Cited By ~ 7

Author(s):

Decha Kumla ◽

José Pereira ◽

Tida Dethoup ◽

Luis Gales ◽

Joana Freitas-Silva ◽

...

Keyword(s):

Antibacterial Activity ◽

Growth Inhibition ◽

Marine Sponge ◽

Multidrug Resistant ◽

Gram Positive ◽

Gram Negative ◽

Chromone Derivatives ◽

Gram Positive Bacteria ◽

Resistant Strains

A previously unreported chromene derivative, 1-hydroxy-12-methoxycitromycin (1c), and four previously undescribed chromone derivatives, including pyanochromone (3b), spirofuranochromone (4), 7-hydroxy-6-methoxy-4-oxo-3-[(1E)-3-oxobut-1-en-1-yl]-4H-chromene-5-carboxylic acid (5), a pyranochromone dimer (6) were isolated, together with thirteen known compounds: β-sitostenone, ergosterol 5,8-endoperoxide, citromycin (1a), 12-methoxycitromycin (1b), myxotrichin D (1d), 12-methoxycitromycetin (1e), anhydrofulvic acid (2a), myxotrichin C (2b), penialidin D (2c), penialidin F (3a), SPF-3059-30 (7), GKK1032B (8) and secalonic acid A (9), from cultures of the marine sponge- associated fungus Penicillium erubescens KUFA0220. Compounds 1a–e, 2a, 3a, 4, 7–9, were tested for their antibacterial activity against Gram-positive and Gram-negative reference and multidrug-resistant strains isolated from the environment. Only 8 exhibited an in vitro growth inhibition of all Gram-positive bacteria whereas 9 showed growth inhibition of methicillin-resistant Staphyllococus aureus (MRSA). None of the compounds were active against Gram-negative bacteria tested.

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In Vitro Activities of Daptomycin, Vancomycin, Linezolid, and Quinupristin-Dalfopristin against Staphylococci and Enterococci, Including Vancomycin- Intermediate and -Resistant Strains

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.4.1062-1066.2000 ◽

2000 ◽

Vol 44 (4) ◽

pp. 1062-1066 ◽

Cited By ~ 237

Author(s):

Michael J. Rybak ◽

Ellie Hershberger ◽

Tabitha Moldovan ◽

Richard G. Grucz

Keyword(s):

Multidrug Resistant ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Vancomycin Resistant Enterococci ◽

Alternative Drug ◽

Potential Alternative ◽

Resistant Strains ◽

Vancomycin Resistant ◽

Time Kill

ABSTRACT The in vitro activity of daptomycin was compared with those of vancomycin, linezolid, and quinupristin-dalfopristin against a variety (n = 203) of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and S. epidermidis (MRSA and MRSE, respectively), vancomycin-resistant enterococci (VRE), and vancomycin-intermediate S. aureus(VISA). Overall, daptomycin was more active against all organisms tested, except Enterococcus faecium and VISA, against which its activity was similar to that of quinupristin-dalfopristin. In time-kill studies with MRSA, MRSE, VRE, and VISA, daptomycin demonstrated greater bactericidal activity than all other drugs tested, killing ≥3 log CFU/ml by 8 h. Daptomycin may be a potential alternative drug therapy for multidrug-resistant gram-positive organisms and warrants further investigation.

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Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies

Molecules ◽

10.3390/molecules27010322 ◽

2022 ◽

Vol 27 (1) ◽

pp. 322

Author(s):

Michio Kurosu ◽

Katsuhiko Mitachi ◽

Junshu Yang ◽

Edward V. Pershing ◽

Bruce D. Horowitz ◽

...

Keyword(s):

Antibacterial Activity ◽

Rose Bengal ◽

Multidrug Resistant ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Skin Cells ◽

Microbial Invasion ◽

Low Concentrations ◽

Resistant Strains ◽

Drug Resistant Strains

Rose bengal has been used in the diagnosis of ophthalmic disorders and liver function, and has been studied for the treatment of solid tumor cancers. To date, the antibacterial activity of rose bengal has been sporadically reported; however, these data have been generated with a commercial grade of rose bengal, which contains major uncontrolled impurities generated by the manufacturing process (80–95% dye content). A high-purity form of rose bengal formulation (HP-RBf, >99.5% dye content) kills a battery of Gram-positive bacteria, including drug-resistant strains at low concentrations (0.01–3.13 μg/mL) under fluorescent, LED, and natural light in a few minutes. Significantly, HP-RBf effectively eradicates Gram-positive bacterial biofilms. The frequency that Gram-positive bacteria spontaneously developed resistance to HP-RB is extremely low (less than 1 × 10−13). Toxicity data obtained through our research programs indicate that HP-RB is feasible as an anti-infective drug for the treatment of skin and soft tissue infections (SSTIs) involving multidrug-resistant (MDR) microbial invasion of the skin, and for eradicating biofilms. This article summarizes the antibacterial activity of pharmaceutical-grade rose bengal, HP-RB, against Gram-positive bacteria, its cytotoxicity against skin cells under illumination conditions, and mechanistic insights into rose bengal’s bactericidal activity under dark conditions.

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Silver Nanoparticles and Their Antibacterial Applications

International Journal of Molecular Sciences ◽

10.3390/ijms22137202 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7202

Author(s):

Tamara Bruna ◽

Francisca Maldonado-Bravo ◽

Paul Jara ◽

Nelson Caro

Keyword(s):

Silver Nanoparticles ◽

Antibacterial Agents ◽

Multidrug Resistant ◽

Secondary Effects ◽

Cytotoxic Effects ◽

Factors Affecting ◽

Gram Positive Bacteria ◽

Resistant Strains

Silver nanoparticles (AgNPs) have been imposed as an excellent antimicrobial agent being able to combat bacteria in vitro and in vivo causing infections. The antibacterial capacity of AgNPs covers Gram-negative and Gram-positive bacteria, including multidrug resistant strains. AgNPs exhibit multiple and simultaneous mechanisms of action and in combination with antibacterial agents as organic compounds or antibiotics it has shown synergistic effect against pathogens bacteria such as Escherichia coli and Staphylococcus aureus. The characteristics of silver nanoparticles make them suitable for their application in medical and healthcare products where they may treat infections or prevent them efficiently. With the urgent need for new efficient antibacterial agents, this review aims to establish factors affecting antibacterial and cytotoxic effects of silver nanoparticles, as well as to expose the advantages of using AgNPs as new antibacterial agents in combination with antibiotic, which will reduce the dosage needed and prevent secondary effects associated to both.

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Sarconesin II, a New Antimicrobial Peptide Isolated from Sarconesiopsis magellanica Excretions and Secretions

Molecules ◽

10.3390/molecules24112077 ◽

2019 ◽

Vol 24 (11) ◽

pp. 2077 ◽

Cited By ~ 1

Author(s):

Andrea Díaz-Roa ◽

Abraham Espinoza-Culupú ◽

Orlando Torres-García ◽

Monamaris M. Borges ◽

Ivan N. Avino ◽

...

Keyword(s):

Micrococcus Luteus ◽

Multidrug Resistant ◽

Peptide Sequence ◽

Resistant Bacteria ◽

Gram Positive ◽

Antimicrobial Drugs ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Conserved Domain ◽

Health Institutions

Antibiotic resistance is at dangerous levels and increasing worldwide. The search for new antimicrobial drugs to counteract this problem is a priority for health institutions and organizations, both globally and in individual countries. Sarconesiopsis magellanica blowfly larval excretions and secretions (ES) are an important source for isolating antimicrobial peptides (AMPs). This study aims to identify and characterize a new S. magellanica AMP. RP-HPLC was used to fractionate ES, using C18 columns, and their antimicrobial activity was evaluated. The peptide sequence of the fraction collected at 43.7 min was determined by mass spectrometry (MS). Fluorescence and electronic microscopy were used to evaluate the mechanism of action. Toxicity was tested on HeLa cells and human erythrocytes; physicochemical properties were evaluated. The molecule in the ES was characterized as sarconesin II and it showed activity against Gram-negative (Escherichia coli MG1655, Pseudomonas aeruginosa ATCC 27853, P. aeruginosa PA14) and Gram-positive (Staphylococcus aureus ATCC 29213, Micrococcus luteus A270) bacteria. The lowest minimum inhibitory concentration obtained was 1.9 μM for M. luteus A270; the AMP had no toxicity in any cells tested here and its action in bacterial membrane and DNA was confirmed. Sarconesin II was documented as a conserved domain of the ATP synthase protein belonging to the Fli-1 superfamily. The data reported here indicated that peptides could be alternative therapeutic candidates for use in infections against Gram-negative and Gram-positive bacteria and eventually as a new resource of compounds for combating multidrug-resistant bacteria.

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Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches

Molecules ◽

10.3390/molecules25122888 ◽

2020 ◽

Vol 25 (12) ◽

pp. 2888 ◽

Cited By ~ 3

Author(s):

Buthaina Jubeh ◽

Zeinab Breijyeh ◽

Rafik Karaman

Keyword(s):

Turning Point ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Gram Positive ◽

Medical Interventions ◽

Gram Positive Bacteria ◽

New Antibiotics ◽

Vancomycin Resistant ◽

New Treatments ◽

Emergence Of Resistance

The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed by the emergence of resistance. The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics. Today, research is active in finding new treatments for multidrug-resistant pathogens. In a step to guide the efforts, the WHO has published a list of the most dangerous bacteria that are resistant to current treatments and requires the development of new antibiotics for combating the resistance. Among the list are various Gram-positive bacteria that are responsible for serious healthcare and community-associated infections. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and drug-resistant Streptococcus pneumoniae are of particular concern. The resistance of bacteria is an evolving phenomenon that arises from genetic mutations and/or acquired genomes. Thus, antimicrobial resistance demands continuous efforts to create strategies to combat this problem and optimize the use of antibiotics. This article aims to provide a review of the most critical resistant Gram-positive bacterial pathogens, their mechanisms of resistance, and the new treatments and approaches reported to circumvent this problem.

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Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

Microorganisms ◽

10.3390/microorganisms8020191 ◽

2020 ◽

Vol 8 (2) ◽

pp. 191 ◽

Cited By ~ 4

Author(s):

Despoina Koulenti ◽

Elena Xu ◽

Andrew Song ◽

Isaac Yin Sum Mok ◽

Drosos E. Karageorgopoulos ◽

...

Keyword(s):

Safety Profile ◽

Bacterial Infections ◽

Antimicrobial Agents ◽

Treatment Options ◽

Multidrug Resistant ◽

Current Treatment ◽

Multi Drug Resistance ◽

Gram Positive ◽

Treatment Regimens ◽

Gram Positive Bacteria

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.

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